The mechanisms causing cell variability in differentiation, development and neoplasia can be examined using the methods of somatic cell genetics. Our goal is to obtain new information about these mechanisms by using embryonal carcinoma cells capable of determination and subsequent differentiation in vitro - an exciting surrogate for the mammalian embryo. Our objectives are: 1) to look for restoration of the ability to differentiate to endoderm among several nullipotent embryonal carcinoma cell lines through various modes of communication with pluripotent cells or other nullipotent lines; 2) to isolate endoderm-deficient variants from the pluripotent "nursed" embronal carcinoma cell line PSA1 and from the "emancipated" lines H6 and OC15S1; 3) to construct complementation groups among multiple variants within each of these lines using hybridization and perhaps cybridization techniques; and 4) to investigate the biological and biochemical nature of the defects in these complementation groups. With these studies we hope to construct eventually a complementation map of the biochemical steps involved in the commitment of pluripotnet embryonic cells to endoderm and to identify these individual steps.